Hearing plays an important role in the normal development of brain structure and function. We have shown that hereditary congenital deafness in cats results in abnormal synaptic structure in auditory nerve terminals, and that synaptic rescue occurs after providing young cats with cochlear implants (Ryugo et al. 2005). These affected synapses initiate circuits implicated in the processing of binaural cues, and will be the subject of the proposed research. Our studies will contribute to knowledge about synaptic plasticity and be pertinent to the increasing number of bilateral cochlear implants that seek to restore the functional benefits of binaural hearing. In theory, bilateral cochlear implants should enrich the acoustic experience by providing cues that contribute to sound localization. Better azimuthal sound localization skills should improve signal discrimination in noise, enhance sound quality, and foster better speech understanding. The brain circuits that mediate these binaural functions are initiated by two classes of auditory nerve endings that in turn establish two separate pathways in the brainstem. One path extracts interaural time differences, whereas the other is specialized for processing interaural intensity differences. Over the next two years, we propose two specific aims to explore the synaptic organization of excitatory and inhibitory inputs involved with these binaural circuits. We will characterize and quantify afferent terminals using electron microscopy and immunocytochemistry to test specific hypotheses regarding how congenital deafness affects binaural circuits by comparing data from normal hearing cats and congenitally deaf cats with or without a cochlear implant. The focus will be on spherical bushy cells and their projections to principal cells of the lateral and medial superior olive, and on globular bushy cells that project to the principal cells of the medial nucleus of the trapezoid body. These aims will evaluate the effect of stimulation via cochlear implants on brain plasticity, and test the hypothesis that some auditory circuits are more amenable to recovery than others. This research utilizes a unique colony of cats expressing hereditary deafness and the generous gift of bilateral cochlear implants from Advanced Bionics Corporation. The results will advance our understanding of the role of cochlear implants and deafness on brain plasticity. The data may also help explain why interaurallevel differences are more salient to bilateral implant users than interaural timing differences. Lastly, the new knowledge could contribute to improved treatment strategies for users of bilateral cochlear implants and impact considerations of auditory brainstem implants.